The proximal half of the mouse chromosome 17, called t-complex, encompasses ~30 Mb of mouse genome and contains many loci that cause abnormalities in embryonic development and male germ cell function, as well as two genes proven to be imprinted (Ifg2r, Mas1). When we placed on the mouse genetic map 155 new genes randomly chosen from the extraembryonic tissues of E7.5 mouse embryos, 10 genes were found clustered in this mouse t-complex. A second series of gene mappings with 800 new genes from preimplantation mouse embryos localized an additional 16 genes to this region. To examine whether these genes may be candidates for t-complex mouse embryonic lethals, these genes were further characterized more in detail.The gene characterized is D17Wsu11e. It was renamed Nucleotide binding protein 2 (Nubp2) because the gene encodes a protein with an ATP/GTP-binding motif. Based on sequence similarity, another gene was cloned and named Nucleotide binding protein 1 (Nubp1). Phylogenetic analyses of the genes, which encode a short form (Nubp2) and long form (Nubp1) of NUBP, clearly establish them as a new NUBP/MRP gene family that is well conserved throughout phylogeny. Mouse Nubp2 is mapped to the t-complex region of mouse Chromosome 17, whereas Nubp1 is mapped to the proximal region of mouse Chromosome 16. Interestingly, both regions are syntenic with human Chromosome 16p13.1-p13.3, suggesting that a chromosomal breakage probably occurred during the evolution of mouse chromosomes between Nubp2 and Nubp1. Knockouts of yeast orthologs of these two genes were not viable, suggestive of the essential functions for these two genes.A second gene analyzed thus far is D17Wsu134e, which was renamed Rsk3 based on the presence of human ortholog, pp90rsk(Ser/Thr) kinase (RSK3). The protein carries two non-identical kinase domains in tandem: the C-terminal kinase is thought to upregulate the N-terminal kinase that phosphorylates the exogenous substrates. Expression of the Rsk3 gene was examined during the mouse development and in different adult organs. A low level of 5.0 kb Rsk3 transcript was observed in E7 embryos. Its expression was dramatically increased at E11 and dropped at E15 and E17 embryos, suggesting a critical function of the gene during mouse development. Among adult tissues, the highest expression was observed in skeletal muscle, but the gene was also expressed in a restricted number of other tissues, including heart, brain, lung, and testis. We are examining possible roles for the mouse Rsk3 gene using anti-sense and gene disruption techniques. - developmental genes; embryonic development; extraembryonic tissue; embryonic lethals